LUX Lung 7 Clinical Trial
LUX-Lung 7 is a randomised, open-label, phase IIb trial of afatinib versus gefitinib as a
first-line treatment of patients with EGFR M+ advanced adenocarcinoma of the lung.
• Adenocarcinoma of the lung
• Stage IIIb/IV
• EGFR mutation (Del19 and/or
L858R) in the tumour tissue
• No prior treatment for
advanced/metastatic disease
• ECOG PS 0-1
1:1 randomisation
afatinib
40 mg oral once daily
until tumour progression
N=319
gefitinib
250 mg once daily
until tumour progression
Median follow-up: 27.4 months
LUX Lung 7 Study Endpoints
Primary endpoints
• Progression-free survival (PFS) by independent review
• Time to treatment failure (TTF): the time from randomisation to
discontinuation for any reason, allowing continuation of treatment
if physicians consider patients to be receiving clinical benefit
• Overall survival (OS)
Secondary endpoints
included
• Objective response rate (ORR)
• Time to and duration of response
• Duration of disease control
• Tumour shrinkage
• Health related quality of life (HRQoL), as reported by EQ-5D
patient questionnaires
LUX Lung 7: 64 sites in 14 countries
Recruitment: Dec 2011-Aug 2013
Canada
31
Germany
14
Spain
25
France
34
Norway
3
Sweden
14
UK
7
Ireland
9
Australia
China
48
Hong Kong
6
Taiwan
22
Korea
56
Singapore
27
19
3
Patient demographics and characteristics were well balanced
between the 2 treatment arms
Afatinib
160, N (%)
Gefitinib
159, N (%)
Total
319, N (%)
63 (30-86)
63 (32-89)
63 (30-89)
Female
91 (56.9)
106 (66.7)
197(61.8)
Male
69 (43.1)
53 (33.3)
122 (38.2)
Asian
94 (58.8)
88 (55.3)
182 (57.1)
Non-Asian*
66 (41.2)
71 (44.7)
137 (42.9)
Brain mets
26 (16.3)
25 (15.7)
51 (16.0)
Never smoker
106 (66.3)
106 (66.7)
212 (66.5)
0
51 (31.9)
47 (29.6)
98 (30.7)
1
109 (68.1)
112 (70.4)
221 (69.3)
IIIB
8 (5.0)
3 (1.9)
11 (3.5)
IV
152 (95.0)
156 ( 98.1)
308 (96.6)
Del19#
93 (58.1)
93 (58.4)
186 (58.3)
L858R
67 (41.9)
66 (41.6)
133 (41.7)
Age, median yrs (min-max)
Gender
Race
Baseline ECOG
NSCLC stage
EGFR mutation
LUX-LUNG 7
Efficacy
Afatinib demonstrated a 27% reduction in relative risk of death
or progression compared to gefitinib
Progression-free survival by independent review (primary endpoint)
Median
(months)
11.0
10.9
1.0
Afatinib® (n=160)
Gefitinib (n=159)
Estimated PFS probability
0.8
Hazard ratio 0.73
(95% CI, 0.57-0.95)
0.6
P=0.0165
27%
vs 15%
18%
0.4
vs 8%
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
Time of progression free survival (months)
• Patients twice as likely to be alive and progression free at 2 years with afatinib vs gefitinib
respectively)
6
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical
Oncology (ESMO) ASIA, Singapore, 20th December 2015.
(18% vs 8%,
Afatinib – PFS benefit consistent across subgroups,
including EGFR mutation type
Progression-free survival by independent review (primary endpoint) prespecified subgroups
Factors
Number of patients
Total
Hazard ratio (95% Cl)
319
0.732 (0.566, 0.947)
133
186
0.708 (0.475, 1.055)
0.764 (0.549, 1.063)
268
51
0.739 (0.560, 0.976)
0.764(0.405, 1.439)
98
221
0.892 (0.542, 1.469)
0.705 (0.524, 0.948)
122
197
0.876 (0.585, 1.312)
0.653 (0.469, 0.910)
177
142
0.681 (0.479, 0.968)
0.845 (0.585, 1.221)
137
182
0.717 (0.487, 1.056)
0.756 (0.539, 1.060)
212
40
67
0.801 (0.584, 1.097)
1.094 (0.559, 2.140)
0.477 (0.270, 0.845)
EGFR mutation
L858R
Del19
Brain métastasés
Absent
Present
Baseline ECOG score
0
1
Gender
Maie
Female
Age group
<65 years
>65 years
Race
Non-Asian
Asian
Smoking hïstory
Never smoked
<15 pack years + stopped >1 year before
Other current or ex-smokers
1/16
Favours afatinib
7
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical
Oncology (ESMO) ASIA, Singapore, 20th December 2015.
1/4
1
4
Favours gefitinib
16
Patients remained on treatment significantly longer with afatinib
than with gefitinib
Time to treatment failure (primary endpoint)
Median
(months)
13.7
11.5
Estimated probability of being free of
treatment failure
1.0
Afatinib® (n=160)
Gefitinib (n=159)
0.8
Hazard ratio 0.73
(95% CI, 0.58-0.92)
0.6
P=0.0073
0.4
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
Time to treatment failure (months)
• 27% significant reduction in relative risk of treatment failure vs gefitinib (P=0.0073)
• Overall survival data not yet mature
TTF is the time from randomisation to discontinuation for any reason, allowing continuation of treatment if physicians consider
patients to be receiving clinical benefit
8
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical
Oncology (ESMO) ASIA, Singapore, 20th December 2015.
42
Afatinib demonstrated significantly improved response rates vs
gefitinib
Objective response by independent review (secondary endpoint)
P=0.0083
Objective response rate (%)
80%
70%
56%
60%
40%
20%
0%
Afatinib
Gefitinib
• Improved objective response and disease control rates vs gefitinib (ORR: 70% vs 56%,
P=0.0083; DCR: 91.3% vs 87.4%)
• Longer duration of response vs gefitinib (10.1 vs 8.4 months, respectively)
9
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical
Oncology (ESMO) ASIA, Singapore, 20th December 2015.
Greater tumour shrinkage in all mutations with afatinib versus
gefitinib
Tumour shrinkage by independent review (secondary endpoint)
Maximum decrease from baseline (%)
40
20
0
-20
-40
-60
Afatinib
-80
Gefitinib
-100
Based on maximum percentage decrease from baseline in the sum of target lesion diameters.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA,
Singapore, 20th December 2015.
All mutations
Greater tumour shrinkage in Del19 mutation patients with afatinib
versus gefitinib
40
20
Afatinib
0
-20
-40
-60
-80
-100
Maximum decrease from baseline (%)
Maximum decrease from baseline (%)
Tumour shrinkage by independent review (secondary endpoint)
Del19 mutations
40
20
Gefitinib
0
-20
-40
-60
-80
-100
≥20% increase
>0 - <30% decrease
≥0 - <20% increase
≥30 - <50% decrease
Based on maximum
11 percentage decrease from baseline in the sum of target lesion diameters.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA,
Singapore, 20th December 2015.
≥50% decrease
Greater tumour shrinkage in L858R mutation patients with afatinib
versus gefitinib
40
20
Afatinib
0
-20
-40
-60
-80
-100
Maximum decrease from baseline (%)
Maximum decrease from baseline (%)
Tumour shrinkage by independent review (secondary endpoint)
L858R mutations
40
20
Gefitinib
0
-20
-40
-60
-80
-100
≥20% increase
>0 - <30% decrease
≥0 - <20% increase
≥30 - <50% decrease
Based on maximum
12 percentage decrease from baseline in the sum of target lesion diameters.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA,
Singapore, 20th December 2015.
≥50% decrease
LUX-LUNG 7
Adverse events
13
Pattern of AEs consistent with the known profiles of
both agents
• The most common AEs were predictable
and generally manageable through
supportive
care and dose reduction
AE=adverse event; ILD=interstitial lung disease.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical
Oncology (ESMO) ASIA, Singapore, 20th December 2015.
AE-related discontinuation
Objective response rate (%)
• Equally low rates of AE-related
discontinuation (6.3% vs 6.3%) with
differing causes; skin-related, diarrhoea
and fatigue for GIOTRIF®, liver enzyme
elevation and ILD for gefitinib
15%
10%
6.3%
6.3%
Afatinib
Gefitinib
5%
0%
14
Pattern of AEs consistent with the known profiles of
both agents
Afatinib
Gefitinib
Related Aes occuring
in >10% patients, n(%)
All Grades
Grade 3
All Grades
Grade 3
Diarrhoea
144 (90.0)
19 (11.9)
97 (61.0)
2 (1.3)
Rash/Acne*
142 (88.8)
15 (9.4)
129 (81.1)
5 (3.1)
Stomatitis*
103 (64.4)
7 (4.4)
38 (23.9)
Paronychia*
89 (55.6)
3 (1.9)
27 (17.0)
Dry skin
52 (32.5)
59 (37.1)
Pruritus
37 (23.1)
36 (22.6)
Fatigue*
33 (20.6)
9 (5.6)
23 (14.5)
Decreased appetite
26 (16.3)
1 (0.6)
19 (11.9)
Nausea
26 (16.3)
2 (1.3)
22 (13.8)
Alopecia
17 (10.6)
24 (15.1)
Vomiting
17 (10.6)
6 (3.8)
1 (0.6)
ALT increase
15 (9.4)
38 (23.9)
12 (7.5)
AST increase
10 (6.3)
33 (20.8)
4 (2.5)
*Preferred terms of AEs.
4 cases of ILD with gefitinib, 3 of them ≥ grade 3, no case of ILD with GIOTRIFR. 1 case of grade 4 diarrhoea with GIOTRIF®,
1 case of grade 4 ALT with gefitinib.
ALT=alanine15
aminotransferase; AST=aspartate transaminase; ILD=interstitial lung disease.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA,
Singapore, 20th December 2015.
1 (0.6)